This invention relates to the treatment of several common skin diseases and premalignant tumors with aliphatic amines having 9 to 18 carbon atoms and pharmaceutically acceptable salts thereof, including hydrohalides. In particular, this invention is a treatment directed against inflammatory and/or hyperproliferative skin diseases in which bacteria or yeasts play a significant adjunctive pathophysiologic role. The present invention resides in the discovery that medium and long chain aliphatic amines and their pharmaceutically acceptable salts effectively treat acne vulgaris, psoriasis, eczema, seborrheic dermatitis, warts, molluscum contagiosum. These compounds may function as primary or adjunctive therapeutic agents.
U.S. Pat. Nos. 4,292,326 (Nazarro-Porro, Sept. 29, 1981) and 4,386,104 (Nazarro-Porro, May 31, 1983) and 4,713,394 (Thornfeldt, Dec. 15, 1987) disclose the use of certain dicarboxylic acids as therapeutic agents for a variety of skin diseases. U.S. Pat. No. 4,067,997 (Kabara, Jan. 10, 1978) discloses the activity against yeast, fungus, and bacteria of a synergistic combination of a 12 carbon atom monocarboxylic acid glycerol ester and a phenolic compound. used as a food preservative.
Acne vulgaris is a multifactorial disease occurring in teenagers and young adults, with inflammatory and noninflammatory comedos on the face and upper trunk. The disease prerequisite is sebaceous glands activated by androgens. For some yet unknown reason hypercornification in the gland duct occurs blocking normal mobility of skin and follicle microorganisms. The restricted environment stimulates release of enzymes (lipases) by Propionobacterium Acnes (an anaerobic corynebacterium). Staphylococcus Epidermidis, and Pitrosporum Ovale (a yeast). Damage to the gland structure and surrounding tissue by the lipases results in inflammatory papules, pustules and cysts, The comedos are free of these microbes. In some, the disease is only manifest as noninflammatory lesions but all patients with inflammatory lesions have some comedos. Major treatments consist of oral and topical antibiotics and retinoids; salicylic acid, sulfu,, and benzoyl peroxide topically, and oral antiandrogen birth control pills.
Psoriasis is a multifactorial disease with epidermal hyperproliferation and epidermal and dermal inflammation producing the lesions. Microbes play an etiologic role since at least 50% of the patients carry Staphylococcus Aureus in the lesions. Beta hemolytic streptococcus is known to cause guttate psoriasis. The psoriasis lesions are sharply demarcated red with thick white scale. They occur predominantly on knees, elbows, scalp, genitalia, and buttocks. Current treatments consist of topical corticosteroids, tar, anthralin, methotrexate azathioprine, etretinate, psoralens plus ultraviolet A light, and tar plus ultraviolet B light.
Eczema is a descriptive term referring to poorly demarcated pruritic, erythematous, scaley, blistered, weeping, fissured or crusted lesions due to many causes. Atopic and numular are the most common types. afflicting any age group. Usually the lesions occur on the face neck, and flexural surfaces. In most patients, there is heavy growth of Staphylococcus Aureus from the lesions of atopic and numular eczema. A purulent rapidly progressive variant, infectious eczematoid, is due to a mixed infection of Staphylococcus Aureus and Streptococcus Pyogenes or either bacteria alone. Current therapy includes topical and systemic corticosteroids. antipruritics, and antibiotics and topical tar.
Warts and molluscum contagiosum are hyperproliferative tumors due to epidermal cell invasion by the Human Papilloma virus and a pox virus, respectively, Unlike other skin virus infections that kill the invaded cells, both these viruses produce hyperplastic, hyperproliferative keratinocytes. Both viruses most commonly infect children. The wart tumors have different morphology depending upon the viral subtype and the thickness of the skin invaded. Molluscum contagiosum are always pearly papules with a central umbilication on an erythematous base. There are currently 23 different chemical and physical destructive treatments, most of which are painful, poorly effective, or may produce systemic toxicity. Poor treatment efficacy in both infections results primarily from the marked tissue hyperplasia induced by the virus. The H.P.V. virus is a proven cancer causing agent.
Seborrheic dermatitis is a histopathologically eczematous dermatosis characterized by poorly demarcated scaley erythematous patches with yellowish greasy scales. "Dandruff" is a mild form of this condition, localized to the scalp. This disease may involve any one, several, or all of the following sites: scalp, eyebrows, glabella, paranasal and chin folds, ears and retroauricular sulci, presternal interscapular regions, pubic regions, and intergluteal folds. Pityrosporum ovale, a yeast, has been shown to play a significant role in 75% of afflicted patients. Present therapy includes corticosteroids, tar, sulfur, and antibiotics, including antiyeast agents.
The conditions described above are the most common skin diseases and tumors, for which it has now been discovered that certain aliphatic amines effectively treat when applied topically. In general, this invention applies to the treatment of inflammatory and hyperproliferative skin diseases in which bacteria play a significant supporting pathophysiologic role.